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Inducing a hibernation-like state in rodents

Some mammals actively lower their body temperature to reduce energy expenditure and ensure survival either by entering a daily torpor (minutes to hours in length) or hibernation (days to weeks) when facing severe food scarcity. Here, Takahashi et al. identify a discrete population of hypothalamic neurons in rodents, characterized by the expression of the neuropeptide QRFP (Q neurons). Pharmacogenetic or optogenetic activation of these Q neurons induces long-lasting (more than 48-hour) hypothermia that is accompanied by an extremely low metabolic state—similar to hibernation. The authors determine the upstream and downstream neurons that are involved in the Q-neuron-induced hypothermia and hypometabolism (QIH), and show the importance of coordinated glutamatergic and GABAergic neurotransmission in Q neurons and the synaptic output of Q-neuron projections in the dorsomedial hypothalamus during QIH. Finally, the researchers show that activation of excitatory Q neurons in rats also induces a QIH-like state. Although mice show daily torpor in response to poor foraging conditions; rats do not, and neither species is a hibernator. It is tempting to hypothesize that should Q neurons exist in people, this would open the door to the development of methods to induce a hypometabolic state, with significant implications in medicine.

Nature Volume 583 Issue 7814

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